Variant chr4-81140668-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP2PP3PP5_Moderate

The NM_006259.3(PRKG2):c.1409T>G(p.Val470Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRKG2
NM_006259.3 missense, splice_region

Scores

Splicing: ADA: 0.4410

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.19

Variant links:

Genes affected

PRKG2 (HGNC:9416): (protein kinase cGMP-dependent 2) This gene encodes a protein that belongs to the serine/threonine protein kinase family of proteins. The encoded protein binds to and inhibits the activation of several receptor tyrosine kinases. The membrane-bound protein is a regulator of intestinal secretion, bone growth and renin secretion. Alternate splicing results in multiple transcript variants encoding distinct isoforms whose regulatory N-termini differ in length but whose C-terminal catalytic domains are identical. [provided by RefSeq, May 2018]

PRKG2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PRKG2. . Gene score misZ 2.9899 (greater than the threshold 3.09). Trascript score misZ 3.189 (greater than threshold 3.09). GenCC has associacion of gene with acromesomelic dysplasia 4.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.748

PP5

Variant 4-81140668-A-C is Pathogenic according to our data. Variant chr4-81140668-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2501812.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG2	NM_006259.3 linkuse as main transcript	c.1409T>G	p.Val470Gly	missense_variant, splice_region_variant	12/19	ENST00000264399.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG2	ENST00000264399.6 linkuse as main transcript	c.1409T>G	p.Val470Gly	missense_variant, splice_region_variant	12/19	5	NM_006259.3	P1	Q13237-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acromesomelic dysplasia 4

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Acualanaylab, Acibadem University

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D;.;T

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.5

.;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.2

D;D;D;.

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.65

MutPred

0.61

.;Loss of stability (P = 0.002);Loss of stability (P = 0.002);.;

MVP

0.75

MPC

1.6

ClinPred

1.0

GERP RS

6.0

Varity_R

0.91

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.44

dbscSNV1_RF

Benign

0.56

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over